Search results for: clinical and patient outcomes
Commenced in January 2007
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Edition: International
Paper Count: 8055

Search results for: clinical and patient outcomes

285 Sustainable Production of Pharmaceutical Compounds Using Plant Cell Culture

Authors: David A. Ullisch, Yantree D. Sankar-Thomas, Stefan Wilke, Thomas Selge, Matthias Pump, Thomas Leibold, Kai Schütte, Gilbert Gorr

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Plants have been considered as a source of natural substances for ages. Secondary metabolites from plants are utilized especially in medical applications but are more and more interesting as cosmetical ingredients and in the field of nutraceuticals. However, supply of compounds from natural harvest can be limited by numerous factors i.e. endangered species, low product content, climate impacts and cost intensive extraction. Especially in the pharmaceutical industry the ability to provide sufficient amounts of product and high quality are additional requirements which in some cases are difficult to fulfill by plant harvest. Whereas in many cases the complexity of secondary metabolites precludes chemical synthesis on a reasonable commercial basis, plant cells contain the biosynthetic pathway – a natural chemical factory – for a given compound. A promising approach for the sustainable production of natural products can be plant cell fermentation (PCF®). A thoroughly accomplished development process comprises the identification of a high producing cell line, optimization of growth and production conditions, the development of a robust and reliable production process and its scale-up. In order to address persistent, long lasting production, development of cryopreservation protocols and generation of working cell banks is another important requirement to be considered. So far the most prominent example using a PCF® process is the production of the anticancer compound paclitaxel. To demonstrate the power of plant suspension cultures here we present three case studies: 1) For more than 17 years Phyton produces paclitaxel at industrial scale i.e. up to 75,000 L in scale. With 60 g/kg dw this fully controlled process which is applied according to GMP results in outstanding high yields. 2) Thapsigargin is another anticancer compound which is currently isolated from seeds of Thapsia garganica. Thapsigargin is a powerful cytotoxin – a SERCA inhibitor – and the precursor for the derivative ADT, the key ingredient of the investigational prodrug Mipsagargin (G-202) which is in several clinical trials. Phyton successfully generated plant cell lines capable to express this compound. Here we present data about the screening for high producing cell lines. 3) The third case study covers ingenol-3-mebutate. This compound is found in the milky sap of the intact plants of the Euphorbiacae family at very low concentrations. Ingenol-3-mebutate is used in Picato® which is approved against actinic keratosis. Generation of cell lines expressing significant amounts of ingenol-3-mebutate is another example underlining the strength of plant cell culture. The authors gratefully acknowledge Inspyr Therapeutics for funding.

Keywords: Ingenol-3-mebutate, plant cell culture, sustainability, thapsigargin

Procedia PDF Downloads 218
284 Effects of the Exit from Budget Support on Good Governance: Findings from Four Sub-Saharan Countries

Authors: Magdalena Orth, Gunnar Gotz

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Background: Domestic accountability, budget transparency and public financial management (PFM) are considered vital components of good governance in developing countries. The aid modality budget support (BS) promotes these governance functions in developing countries. BS engages in political decision-making and provides financial and technical support to poverty reduction strategies of the partner countries. Nevertheless, many donors have withdrawn their support from this modality due to cases of corruption, fraud or human rights violations. This exit from BS is leaving a finance and governance vacuum in the countries. The evaluation team analyzed the consequences of terminating the use of this modality and found particularly negative effects for good governance outcomes. Methodology: The evaluation uses a qualitative (theory-based) approach consisting of a comparative case study design, which is complemented by a process-tracing approach. For the case studies, the team conducted over 100 semi-structured interviews in Malawi, Uganda, Rwanda and Zambia and used four country-specific, tailor-made budget analysis. In combination with a previous DEval evaluation synthesis on the effects of BS, the team was able to create a before-and-after comparison that yields causal effects. Main Findings: In all four countries domestic accountability and budget transparency declined if other forms of pressure are not replacing BS´s mutual accountability mechanisms. In Malawi a fraud scandal created pressure from the society and from donors so that accountability was improved. In the other countries, these pressure mechanisms were absent so that domestic accountability declined. BS enables donors to actively participate in political processes of the partner country as donors transfer funds into the treasury of the partner country and conduct a high-level political dialogue. The results confirm that the exit from BS created a governance vacuum that, if not compensated through external/internal pressure, leads to a deterioration of good governance. For example, in the case of highly aid dependent Malawi did the possibility of a relaunch of BS provide sufficient incentives to push for governance reforms. Overall the results show that the three good governance areas are negatively affected by the exit from BS. This stands in contrast to positive effects found before the exit. The team concludes that the relationship is causal, because the before-and-after comparison coherently shows that the presence of BS correlates with positive effects and the absence with negative effects. Conclusion: These findings strongly suggest that BS is an effective modality to promote governance and its abolishment is likely to cause governance disruptions. Donors and partner governments should find ways to re-engage in closely coordinated policy-based aid modalities. In addition, a coordinated and carefully managed exit-strategy should be in place before an exit from similar modalities is considered. Particularly a continued framework of mutual accountability and a high-level political dialogue should be aspired to maintain pressure and oversight that is required to achieve good governance.

Keywords: budget support, domestic accountability, public financial management and budget transparency, Sub-Sahara Africa

Procedia PDF Downloads 115
283 Indigenous Pre-Service Teacher Education: Developing, Facilitating, and Maintaining Opportunities for Retention and Graduation

Authors: Karen Trimmer, Raelene Ward, Linda Wondunna-Foley

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Within Australian tertiary institutions, the subject of Aboriginal and Torres Strait Islander education has been a major concern for many years. Aboriginal and Torres Strait Islander teachers are significantly under-represented in Australian schools and universities. High attrition rates in teacher education and in the teaching industry have contributed to a minimal growth rate in the numbers of Aboriginal and Torres Strait Islander teachers in previous years. There was an increase of 500 Indigenous teachers between 2001 and 2008 but these numbers still only account for one percent of teaching staff in government schools who identified as Aboriginal and Torres Strait Islander Australians (Ministerial Council for Education, Early Childhood Development and Youth Affairs 2010). Aboriginal and Torres Strait Islander teachers are paramount in fostering student engagement and improving educational outcomes for Indigenous students. Increasing the numbers of Aboriginal and Torres Strait Islander teachers is also a key factor in enabling all students to develop understanding of and respect for Aboriginal and Torres Strait Islander histories, cultures, and language. An ambitious reform agenda to improve the recruitment and retention of Aboriginal and Torres Strait Islander teachers will be effective only through national collaborative action and co-investment by schools and school authorities, university schools of education, professional associations, and Indigenous leaders and community networks. Whilst the University of Southern Queensland currently attracts Indigenous students to its teacher education programs (61 students in 2013 with an average of 48 enrollments each year since 2010) there is significant attrition during pre-service training. The annual rate of exiting before graduation remains high at 22% in 2012 and was 39% for the previous two years. These participation and retention rates are consistent with other universities across Australia. Whilst aspirations for a growing number of Indigenous people to be trained as teachers is present, there is a significant loss of students during their pre-service training and within the first five years of employment as a teacher. These trends also reflect the situation where Aboriginal and Torres Strait Islander teachers are significantly under-represented, making up less than 1% of teachers in schools across Australia. Through a project conducted as part the nationally funded More Aboriginal and Torres Strait Islander Teachers Initiative (MATSITI) we aim to gain an insight into the reasons that impact Aboriginal and Torres Strait Islander student’s decisions to exit their program. Through the conduct of focus groups and interviews with two graduating cohorts of self-identified Aboriginal and Torres Strait Islander students, rich data has been gathered to gain an understanding of the barriers and enhancers to the completion of pre-service qualification and transition to teaching. Having a greater understanding of these reasons then allows the development of collaborative processes and procedures to increase retention and completion rates of new Indigenous teachers. Analysis of factors impacting on exit decisions and transitions has provided evidence to support change of practice, redesign and enhancement of relevant courses and development of policy/procedures to address identified issues.

Keywords: graduation, indigenous, pre-service teacher education, retention

Procedia PDF Downloads 439
282 A Demonstration of How to Employ and Interpret Binary IRT Models Using the New IRT Procedure in SAS 9.4

Authors: Ryan A. Black, Stacey A. McCaffrey

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Over the past few decades, great strides have been made towards improving the science in the measurement of psychological constructs. Item Response Theory (IRT) has been the foundation upon which statistical models have been derived to increase both precision and accuracy in psychological measurement. These models are now being used widely to develop and refine tests intended to measure an individual's level of academic achievement, aptitude, and intelligence. Recently, the field of clinical psychology has adopted IRT models to measure psychopathological phenomena such as depression, anxiety, and addiction. Because advances in IRT measurement models are being made so rapidly across various fields, it has become quite challenging for psychologists and other behavioral scientists to keep abreast of the most recent developments, much less learn how to employ and decide which models are the most appropriate to use in their line of work. In the same vein, IRT measurement models vary greatly in complexity in several interrelated ways including but not limited to the number of item-specific parameters estimated in a given model, the function which links the expected response and the predictor, response option formats, as well as dimensionality. As a result, inferior methods (a.k.a. Classical Test Theory methods) continue to be employed in efforts to measure psychological constructs, despite evidence showing that IRT methods yield more precise and accurate measurement. To increase the use of IRT methods, this study endeavors to provide a comprehensive overview of binary IRT models; that is, measurement models employed on test data consisting of binary response options (e.g., correct/incorrect, true/false, agree/disagree). Specifically, this study will cover the most basic binary IRT model, known as the 1-parameter logistic (1-PL) model dating back to over 50 years ago, up until the most recent complex, 4-parameter logistic (4-PL) model. Binary IRT models will be defined mathematically and the interpretation of each parameter will be provided. Next, all four binary IRT models will be employed on two sets of data: 1. Simulated data of N=500,000 subjects who responded to four dichotomous items and 2. A pilot analysis of real-world data collected from a sample of approximately 770 subjects who responded to four self-report dichotomous items pertaining to emotional consequences to alcohol use. Real-world data were based on responses collected on items administered to subjects as part of a scale-development study (NIDA Grant No. R44 DA023322). IRT analyses conducted on both the simulated data and analyses of real-world pilot will provide a clear demonstration of how to construct, evaluate, and compare binary IRT measurement models. All analyses will be performed using the new IRT procedure in SAS 9.4. SAS code to generate simulated data and analyses will be available upon request to allow for replication of results.

Keywords: instrument development, item response theory, latent trait theory, psychometrics

Procedia PDF Downloads 329
281 A Resilience-Based Approach for Assessing Social Vulnerability in New Zealand's Coastal Areas

Authors: Javad Jozaei, Rob G. Bell, Paula Blackett, Scott A. Stephens

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In the last few decades, Social Vulnerability Assessment (SVA) has been a favoured means in evaluating the susceptibility of social systems to drivers of change, including climate change and natural disasters. However, the application of SVA to inform responsive and practical strategies to deal with uncertain climate change impacts has always been challenging, and typically agencies resort back to conventional risk/vulnerability assessment. These challenges include complex nature of social vulnerability concepts which influence its applicability, complications in identifying and measuring social vulnerability determinants, the transitory social dynamics in a changing environment, and unpredictability of the scenarios of change that impacts the regime of vulnerability (including contention of when these impacts might emerge). Research suggests that the conventional quantitative approaches in SVA could not appropriately address these problems; hence, the outcomes could potentially be misleading and not fit for addressing the ongoing uncertain rise in risk. The second phase of New Zealand’s Resilience to Nature’s Challenges (RNC2) is developing a forward-looking vulnerability assessment framework and methodology that informs the decision-making and policy development in dealing with the changing coastal systems and accounts for complex dynamics of New Zealand’s coastal systems (including socio-economic, environmental and cultural). Also, RNC2 requires the new methodology to consider plausible drivers of incremental and unknowable changes, create mechanisms to enhance social and community resilience; and fits the New Zealand’s multi-layer governance system. This paper aims to analyse the conventional approaches and methodologies in SVA and offer recommendations for more responsive approaches that inform adaptive decision-making and policy development in practice. The research adopts a qualitative research design to examine different aspects of the conventional SVA processes, and the methods to achieve the research objectives include a systematic review of the literature and case study methods. We found that the conventional quantitative, reductionist and deterministic mindset in the SVA processes -with a focus the impacts of rapid stressors (i.e. tsunamis, floods)- show some deficiencies to account for complex dynamics of social-ecological systems (SES), and the uncertain, long-term impacts of incremental drivers. The paper will focus on addressing the links between resilience and vulnerability; and suggests how resilience theory and its underpinning notions such as the adaptive cycle, panarchy, and system transformability could address these issues, therefore, influence the perception of vulnerability regime and its assessment processes. In this regard, it will be argued that how a shift of paradigm from ‘specific resilience’, which focuses on adaptive capacity associated with the notion of ‘bouncing back’, to ‘general resilience’, which accounts for system transformability, regime shift, ‘bouncing forward’, can deliver more effective strategies in an era characterised by ongoing change and deep uncertainty.

Keywords: complexity, social vulnerability, resilience, transformation, uncertain risks

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280 Anti-tuberculosis, Resistance Modulatory, Anti-pulmonary Fibrosis and Anti-silicosis Effects of Crinum Asiaticum Bulbs and Its Active Metabolite, Betulin

Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

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279 Training Hearing Parents in SmiLE Therapy Supports the Maintenance and Generalisation of Deaf Children's Social Communication Skills

Authors: Martina Curtin, Rosalind Herman

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Background: Deaf children can experience difficulties with understanding how social interaction works, particularly when communicating with unfamiliar hearing people. Deaf children often struggle with integrating into a mainstream, hearing environments. These negative experiences can lead to social isolation, depression and other mental health difficulties later in life. smiLE Therapy (Schamroth, 2015) is a video-based social communication intervention that aims to teach deaf children skills to confidently communicate with unfamiliar hearing people. Although two previous studies have reported improvements in communication skills immediately post intervention, evidence for maintenance of gains or generalisation of skills (i.e., the transfer of newly learnt skills to untrained situations) has not to date been demonstrated. Parental involvement has been shown to support deaf children’s therapy outcomes. Therefore, this study added parent training to the therapy children received to investigate the benefits to generalisation of children’s skills. Parents were also invited to present their perspective on the training they received. Aims: (1) To assess pupils’ progress from pre- to post-intervention in trained and untrained tasks, (2) to investigate if training parents improved their (a) understanding of their child’s needs and (b) their skills in supporting their child appropriately in smiLE Therapy tasks, (3) to assess if parent training had an impact on the pupil’s ability to (a) maintain their skills in trained tasks post-therapy, and (b) generalise their skills in untrained, community tasks. Methods: This was a mixed-methods, repeated measures study. 31 deaf pupils (aged between 7 and 14) received an hour of smiLE Therapy per week, for 6 weeks. Communication skills were assessed pre-, post- and 3-months post-intervention using the Communication Skills Checklist. Parents were then invited to attend two training sessions and asked to bring a video of their child communicating in a shop or café. These videos were used to assess whether, after parent training, the child was able to generalise their skills to a new situation. Finally, parents attended a focus group to discuss the effectiveness of the therapy, particularly the wider impact, i.e., more child participation within the hearing community. Results: All children significantly improved their scores following smiLE therapy and maintained these skills to high level. Children generalised a high percentage of their newly learnt skills to an untrained situation. Parents reported improved understanding of their child’s needs, their child’s potential and in how to support them in real-life situations. Parents observed that their children were more confident and independent when carrying out communication tasks with unfamiliar hearing people. Parents realised they needed to ‘let go’ and embrace their child’s independence and provide more opportunities for them to participate in their community. Conclusions: This study adds to the evidence base on smiLE Therapy; it is an effective intervention that develops deaf children’s ability to interact competently with unfamiliar, hearing, communication partners. It also provides preliminary evidence of the benefits of parent training in helping children to generalise their skills to other situations. These findings will be of value to therapists wishing to develop deaf children’s communication skills beyond the therapy setting.

Keywords: deaf children, generalisation, parent involvement, social communication

Procedia PDF Downloads 118
278 The Effectiveness of Prenatal Breastfeeding Education on Breastfeeding Uptake Postpartum: A Systematic Review.

Authors: Jennifer Kehinde, Claire O'donnell, Annmarie Grealish

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Introduction: Breastfeeding has been shown to provide numerous health benefits for both infants and mothers. The decision to breastfeed is influenced by physiological, psychological, and emotional factors. However, the importance of equipping mothers with the necessary knowledge for successful breastfeeding practice cannot be ruled out. The decline in global breastfeeding rate can be linked to lack of adequate breastfeeding education during prenatal stage.This systematic review examined the effectiveness of prenatal breastfeeding education on breastfeeding uptake postpartum. Method: This review was undertaken and reported in conformity with the Preferred Reporting Items for Systemic Reviews and Meta-Analysis statement (PRISMA) and was registered on the international prospective register for systematic reviews (PROSPERO: CRD42020213853). A PICO analysis (population, intervention, comparison, outcome) was undertaken to inform the choice of keywords in the search strategy to formulate the review question which was aimed at determining the effectiveness of prenatal breastfeeding educational programs at improving breastfeeding uptake following birth. A systematic search of five databases (Cumulative Index to Nursing and Allied Health Literature, Medline, Psych INFO, and Applied Social Sciences Index and Abstracts) were searched between January 2014 until July 2021 to identify eligible studies. Quality assessment and narrative synthesis were subsequently undertaken. Results: Fourteen studies were included. All 14 studies used different types of breastfeeding programs; eight used a combination of curriculum based breastfeeding education program, group prenatal breastfeeding counselling and one-to-one breastfeeding educational programs which were all delivered in person; four studies used web-based learning platforms to deliver breastfeeding education prenatally which were both delivered online and face to face over a period of 3 weeks to 2 months with follow-up periods ranging from 3 weeks to 6 months; one study delivered breastfeeding educational intervention using mother-to-mother breastfeeding support groups in promoting exclusive breastfeeding and one study disseminated breastfeeding education to participants based on the theory of planned behaviour. The most effective interventions were those that included both theory and hands-on demonstrations. Results showed an increase in breastfeeding uptake, breastfeeding knowledge, increase in positive attitude to breastfeeding and an increase in maternal breastfeeding self-efficacy among mothers who participated in breastfeeding educational programs during prenatal care. Conclusion: Prenatal breastfeeding education increases women’s knowledge of breastfeeding. Mothers who are knowledgeable about breastfeeding and hold a positive approach towards breastfeeding have the tendency to initiate breastfeeding and continue for a lengthened period. Findings demonstrates a general correlation between prenatal breastfeeding education and increased breastfeeding uptake postpartum. The high level of positive breastfeeding outcome inherent in all the studies can be attributed to prenatal breastfeeding education. This review provides rigorous contemporary evidence that healthcare professionals and policymakers can apply when developing effective strategies to improve breastfeeding rates and ultimately improve the health outcomes of mothers and infants.

Keywords: breastfeeding, breastfeeding programs, breastfeeding self-efficacy, prenatal breastfeedng education

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277 Feasibility of Applying a Hydrodynamic Cavitation Generator as a Method for Intensification of Methane Fermentation Process of Virginia Fanpetals (Sida hermaphrodita) Biomass

Authors: Marcin Zieliński, Marcin Dębowski, Mirosław Krzemieniewski

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The anaerobic degradation of substrates is limited especially by the rate and effectiveness of the first (hydrolytic) stage of fermentation. This stage may be intensified through pre-treatment of substrate aimed at disintegration of the solid phase and destruction of substrate tissues and cells. The most frequently applied criterion of disintegration outcomes evaluation is the increase in biogas recovery owing to the possibility of its use for energetic purposes and, simultaneously, recovery of input energy consumed for the pre-treatment of substrate before fermentation. Hydrodynamic cavitation is one of the methods for organic substrate disintegration that has a high implementation potential. Cavitation is explained as the phenomenon of the formation of discontinuity cavities filled with vapor or gas in a liquid induced by pressure drop to the critical value. It is induced by a varying field of pressures. A void needs to occur in the flow in which the pressure first drops to the value close to the pressure of saturated vapor and then increases. The process of cavitation conducted under controlled conditions was found to significantly improve the effectiveness of anaerobic conversion of organic substrates having various characteristics. This phenomenon allows effective damage and disintegration of cellular and tissue structures. Disintegration of structures and release of organic compounds to the dissolved phase has a direct effect on the intensification of biogas production in the process of anaerobic fermentation, on reduced dry matter content in the post-fermentation sludge as well as a high degree of its hygienization and its increased susceptibility to dehydration. A device the efficiency of which was confirmed both in laboratory conditions and in systems operating in the technical scale is a hydrodynamic generator of cavitation. Cavitators, agitators and emulsifiers constructed and tested worldwide so far have been characterized by low efficiency and high energy demand. Many of them proved effective under laboratory conditions but failed under industrial ones. The only task successfully realized by these appliances and utilized on a wider scale is the heating of liquids. For this reason, their usability was limited to the function of heating installations. Design of the presented cavitation generator allows achieving satisfactory energy efficiency and enables its use under industrial conditions in depolymerization processes of biomass with various characteristics. Investigations conducted on the laboratory and industrial scale confirmed the effectiveness of applying cavitation in the process of biomass destruction. The use of the cavitation generator in laboratory studies for disintegration of sewage sludge allowed increasing biogas production by ca. 30% and shortening the treatment process by ca. 20 - 25%. The shortening of the technological process and increase of wastewater treatment plant effectiveness may delay investments aimed at increasing system output. The use of a mechanical cavitator and application of repeated cavitation process (4-6 times) enables significant acceleration of the biogassing process. In addition, mechanical cavitation accelerates increases in COD and VFA levels.

Keywords: hydrodynamic cavitation, pretreatment, biomass, methane fermentation, Virginia fanpetals

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276 Wealth-Based Inequalities in Child Health: A Micro-Level Analysis of Maharashtra State in India

Authors: V. Rekha, Rama Pal

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The study examines the degree and magnitude of wealth-based inequalities in child health and its determinants in India. Despite making strides in economic growth, India has failed to secure a better nutritional status for all the children. The country currently faces the double burden of malnutrition as well as the problems of overweight and obesity. Child malnutrition, obesity, unsafe water, sanitation among others are identified as the risk factors for Non-Communicable Diseases (NCDs). Eliminating malnutrition in all its forms will catalyse improved health and economic outcomes. The assessment of the distributive dimension of child health across various segments of the population is essential for effective policy intervention. The study utilises the fourth round of District Level Health Survey for 2012-13 to analyse the inequalities among children in the age group 0-14 years in Maharashtra, a state in the western region of India with a population of 11.24 crores which constitutes 9.3 percent of the total population of India. The study considers the extent of health inequality by state, districts, sector, age-groups, and gender. The z-scores of four child health outcome variables are computed to assess the nutritional status of pre-school and school children using WHO reference. The descriptive statistics, concentration curves, concentration indices, correlation matrix, logistic regression have been used to analyse the data. The results indicate that magnitude of inequality is higher in Maharashtra and child health inequalities manifest primarily among the weaker sections of society. The concentration curves show that there exists a pro-poor inequality in child malnutrition measured by stunting, wasting, underweight, anaemia and a pro-rich overweight inequality. The inequalities in anaemia are observably lower due to the widespread prevalence. Rural areas exhibit a higher incidence of malnutrition, but greater inequality is observed in the urban areas. Overall, the wealth-based inequalities do not vary significantly between age groups. It appears that there is no gender discrimination at the state level. Further, rural-urban differentials in gender show that boys from the rural area and girls living in the urban region experience higher disparities in health. The relative distribution of undernutrition across districts in Maharashtra reveals that malnutrition is rampant and considerable heterogeneity also exists. A negative correlation is established between malnutrition prevalence and human development indicators. The findings of logistic regression analysis reveal that lower economic status of the household is associated with a higher probability of being malnourished. The study recognises household wealth, education of the parent, child gender, and household size as factors significantly related to malnutrition. The results suggest that among the supply-side variables, child-oriented government programmes might be beneficial in tackling nutrition deficit. In order to bridge the health inequality gap, the government needs to target the schemes better and should expand the coverage of services.

Keywords: child health, inequality, malnutrition, obesity

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275 Valuing Academic Excellence in Higher Education: The Case of Establishing a Human Development Unit in a European Start-up University

Authors: Eleftheria Atta, Yianna Vovides, Marios Katsioloudes

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In the fusion of neoliberalism and globalization, Higher Education (HE) is becoming increasingly complex. The changing patterns of the economy worldwide caused the development of high value-added economy HE has been viewed as a social investment, significant for the development of knowledge-based societies and economies. In order to contribute to economic competitiveness universities are required to produce local and employable workers in order to fit into the neoliberal economic environment. The emergence of neoliberal performativity, which measures outcomes, is a key aspect in a neoliberal era. It facilitates the redesign of institutions making organizations and individuals to think about themselves in relation to their performance. Performativity and performance management systems lead academics to become more effective, professionally advance, improve and become better than others and therefore act competitively. Besides the aforementioned complexities, universities also encounter the challenge of maintaining a set of values to guide an institution’s actions and which have always been highly respected in developing a HE institution. The formulation of a clear set of values also determines the institutional culture which will be maintained. It is evident that values create a significant framework for the workplace and may determine positive institutional results. Universities are required to engage in activities for capacity building which will improve their students’ competence as well as offer opportunities to administrative and academic staff to professionally develop in light of neoliberal performativity. Additionally, the University is now considered as an innovation ecosystem playing a significant role in providing education, research and innovation to help create solutions to meet social, environmental and economic challenges. Thus, Universities become central in orchestrating multi-actor innovation networks. This presentation will discuss the establishment of an institutional unit entitled ‘Human Development Unit’ (HDU) in a European start-up university. The activities of the HDU are envisioned as drivers for innovation that would enable the university as a whole to maintain its position in a fast-changing world and be ready to face adaptive challenges. In addition, the HDU provides its students, staff, and faculty with opportunities to advance their academic and professional development through engagement in programs that align with institutional values. It also serves as a connector with the broader community. The presentation will highlight the functions of three centers which the unit will coordinate namely, the Student Development Center (SDC), the Faculty & Staff Development Center (FSDC) and the Continuing Education Center (CEC). The presentation aligns with the aim of the conference as it welcomes presentations to discuss innovations and challenges encountered in HE. Particularly, this presentation seeks to discuss the establishment of an innovative unit at a start-up university which will contribute to creating an institutional culture shaped by the value of academic excellence for students as well as for staff, shaping and defining the functions and activities of the unit. The establishment of the proposed unit is crucial in a start-up university both to differentiate from other competitors but also to sustain its presence given the pressures in a neoliberal HE context.

Keywords: academic excellence, globalization, human development unit, neoliberalism

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274 Gender Differences In Pain Assessment: A Daily Activities Perspective

Authors: Hui-mei Huang, Huei-Jiun Cheng

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Introduction Many patients are aware of the health benefits associated with an active lifestyle, but they are often hindered from engaging in physical activity due to the presence of pain. The majority of patients experience pain, which can fluctuate over time and is influenced by various factors, including gender. Gender differences in clinical pain and pain-related conditions are widely recognized. Existing literature strongly supports the notion that men and women exhibit distinct responses to pain. Previous studies conducted in Taiwan have highlighted gender differences in pain assessment, but only a limited number of studies have investigated the gender-related factors that influence pain during daily activities. The objective of this study was to examine gender differences in pain assessment among inpatients in Taiwan and investigate whether gender and surgical procedures are factors that impact the daily activities of pain. Method In this study, a prospective and structured questionnaire survey method was utilized, employing intentional sampling to gather data from inpatients admitted to a medical center in central Taiwan. The research period covered in this study is from October 1, 2019, to June 30, 2020. In this study, participants who were hospitalized within 48 hours were requested to self-assess their pain using the Numeric Rating Scale (NRS) and indicate the impact of pain on their activities. The data were analyzed to explore the potential influence of gender and surgical procedures on daily activities affected by pain. Result A total of 722 cases were included in the study, with the mean age of the subjects is 54.38 years old (SD=16.3), and the range varied from 18 to 93 years old. Among the subjects, 48.23% (n=348) were male, and 62.3% (n=450) of them had received more than 12 years of education., and 56.9% (n=411) underwent surgery. The results indicated that regardless of whether the participants underwent surgery or not, females experienced higher perceived severe pain intensity than males (t=2.248, P < .05). However, in surgical patients, there was no significant difference in gender (t=1.75, P > .05). Regarding the impact of pain on daily activities when pain intensity reached 7 , male subjects experienced a 5-point effect on their daily activities (AUC=0.84, 95% CI 0.79-0.89, P <0.01), while female subjects experienced a 7-point effect (AUC=0.88, 95% CI 0.80-0.87, P <0.01). Discussion Some studies suggest that women experience painful stimuli as more intense than men, this difference has been observed in various types of experimental pain, including mechanical and thermal stimuli. Our study reached the same conclusion, female patients exhibited greater intensity of pain. According to the research findings, The research findings highlight the significant impact of gender on individuals' response to intense pain (NRS>7) during their daily activities, with men showing a higher pain tolerance. The higher pain tolerance often observed in men may be attributed to societal conditioning, which encourages them to conceal outward expressions of pain. Further research in this area could help provide a more comprehensive understanding of the topic in Taiwan.

Keywords: pain assessment, gender, surgery, activities of daily living

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273 Antimicrobial Value of Olax subscorpioidea and Bridelia ferruginea on Micro-Organism Isolates of Dental Infection

Authors: I. C. Orabueze, A. A. Amudalat, S. A. Adesegun, A. A. Usman

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Dental and associated oral diseases are increasingly affecting a considerable portion of the population and are considered some of the major causes of tooth loss, discomfort, mouth odor and loss of confidence. This study focused on the ethnobotanical survey of medicinal plants used in oral therapy and evaluation of the antimicrobial activities of methanolic extracts of two selected plants from the survey for their efficacy against dental microorganisms. The ethnobotanical survey was carried out in six herbal markets in Lagos State, Nigeria by oral interviewing and information obtained from an old family manually complied herbal medication book. Methanolic extracts of Olax subscorpioidea (stem bark) and Bridelia ferruginea (stem bark) were assayed for their antimicrobial activities against clinical oral isolates (Aspergillus fumigatus, Candida albicans, Streptococcus spp, Staphylococcus aureus, Lactobacillus acidophilus and Pseudomonas aeruginosa). In vitro microbial technique (agar well diffusion method and minimum inhibitory concentration (MIC) assay) were employed for the assay. Chlorhexidine gluconate was used as the reference drug for comparison with the extract results. And the preliminary phytochemical screening of the constituents of the plants were done. The ethnobotanical survey produced plants (28) of diverse family. Different parts of plants (seed, fruit, leaf, root, bark) were mentioned but 60% mentioned were either the stem or the bark. O. subscorpioidea showed considerable antifungal activity with zone of inhibition ranging from 2.650 – 2.000 cm against Aspergillus fumigatus but no such encouraging inhibitory activity was observed in the other assayed organisms. B. ferruginea showed antibacterial sensitivity against Streptococcus spp, Staphylococcus aureus, Lactobacillus acidophilus and Pseudomonas aeruginosa with zone of inhibitions ranging from 3.400 - 2.500, 2.250 - 1.600, 2.700 - 1.950, 2.225 – 1.525 cm respectively. The minimum inhibitory concentration of O. subscorpioidea against Aspergillus fumigatus was 51.2 mg ml-1 while that of B. ferruginea against Streptococcus spp was 0.1mg ml-1 and for Staphylococcus aureus, Lactobacillus acidophilus and Pseudomonas aeruginosa were 25.6 mg ml-1. A phytochemical analysis reveals the presence of alkaloids, saponins, cardiac glycoside, tannins, phenols and terpenoids in both plants, with steroids only in B. ferruginea. No toxicity was observed among mice given the two methanolic extracts (1000 mg Kg-1) after 21 days. The barks of both plants exhibited antimicrobial properties against periodontal diseases causing organisms assayed, thus up-holding their folkloric use in oral disorder management. Further research could be done viewing these extracts as combination therapy, checking for possible synergistic value in toothpaste and oral rinse formulations for reducing oral bacterial flora and fungi load.

Keywords: antimicrobial activities, Bridelia ferruginea, dental disinfection, methanolic extract, Olax subscorpioidea, ethnobotanical survey

Procedia PDF Downloads 218
272 Visual Preferences of Elementary School Children with Autism Spectrum Disorder: An Experimental Study

Authors: Larissa Pliska, Isabel Neitzel, Michael Buschermöhle, Olga Kunina-Habenicht, Ute Ritterfeld

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Visual preferences that can be assessed via eye tracking technologies are considered one of the defining hallmarks of Autism Spectrum Disorder (ASD). Specifically, children with ASD show a decreased preference for social compared to geometric images compared to typically developed (TD) children. Such differences are already prevalent at a very early age and indicate the severity of the disorder: toddlers with ASD who preferred the geometric images when presented with social and geometric images also showed higher ASD symptom severity than toddlers with ASD who showed higher social attention. Furthermore, the complexity of social pictures (one child playing vs. two children playing together) as well as the mode of stimulus presentation (video or image), appear to have no influence on the hallmark. Although such visual preferences are also a hallmark of the diagnosis of ASD, studies have primarily been conducted with toddlers and preschool children. Since the age for diagnosis often falls into this age group – the average age of diagnosis for ASD in Germany is 6.5 years – we were investigating whether visual preferences (1) persist into this age range and (2) might be used for a technology-based screening. We examined the visual preferences of 16 boys aged 6 to 11 with ASD and normal cognition and TD children (1:1 matching) within an experimental setting. Matching criteria are the children's age and the parent's level of education. Different stimulus presentation formats (images vs. videos) and different levels of stimulus complexity are included. Children with and without ASD always receive pairs of social and non-social images and video stimuli on a screen. For images, the social stimuli show one or more children playing whereas the non-social show images of the universe. For videos, the social stimuli show a man or a woman making faces, and the non-social are dynamic geometric shapes. During stimulus presentation of approx. 10 s length by image and of approx. 18 s length by video, eye movements (i.e., eye position and gaze direction) are captured. Therefore, KIZMO GmbH developed a customized, native iOS app (KIZMO Face-Analyzer) for use on iPads. In addition, the preferences of the image stimuli are directly measured. Data collection is currently ongoing, with an expected sample size of 32 (16 children with ASD and 16 TD children). One expected finding is that children with ASD demonstrate lower attention (total fixation time) on social stimuli (images and video) compared to their TD peers, even at this elementary school age. We also expect that the stimulus presentation, including different complexity levels, will not affect social attention. The data for the group of children with ASD is already available, while the data for the control group will be collected in the coming months. Preliminary descriptive analyses for 16 children with ASD show that in 80 possible image comparisons 52 times the non-social one was selected, 8 times the social one and 20 are missing or cannot be correctly assigned. The results will be discussed concerning various clinical implications, e.g. implementation of an automated digital screening.

Keywords: autism spectrum disorder, visual preference, hallmark, eye movement

Procedia PDF Downloads 27
271 A 1H NMR-Linked PCR Modelling Strategy for Tracking the Fatty Acid Sources of Aldehydic Lipid Oxidation Products in Culinary Oils Exposed to Simulated Shallow-Frying Episodes

Authors: Martin Grootveld, Benita Percival, Sarah Moumtaz, Kerry L. Grootveld

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Objectives/Hypotheses: The adverse health effect potential of dietary lipid oxidation products (LOPs) has evoked much clinical interest. Therefore, we employed a 1H NMR-linked Principal Component Regression (PCR) chemometrics modelling strategy to explore relationships between data matrices comprising (1) aldehydic LOP concentrations generated in culinary oils/fats when exposed to laboratory-simulated shallow frying practices, and (2) the prior saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acid (PUFA) contents of such frying media (FM), together with their heating time-points at a standard frying temperature (180 oC). Methods: Corn, sunflower, extra virgin olive, rapeseed, linseed, canola, coconut and MUFA-rich algae frying oils, together with butter and lard, were heated according to laboratory-simulated shallow-frying episodes at 180 oC, and FM samples were collected at time-points of 0, 5, 10, 20, 30, 60, and 90 min. (n = 6 replicates per sample). Aldehydes were determined by 1H NMR analysis (Bruker AV 400 MHz spectrometer). The first (dependent output variable) PCR data matrix comprised aldehyde concentration scores vectors (PC1* and PC2*), whilst the second (predictor) one incorporated those from the fatty acid content/heating time variables (PC1-PC4) and their first-order interactions. Results: Structurally complex trans,trans- and cis,trans-alka-2,4-dienals, 4,5-epxy-trans-2-alkenals and 4-hydroxy-/4-hydroperoxy-trans-2-alkenals (group I aldehydes predominantly arising from PUFA peroxidation) strongly and positively loaded on PC1*, whereas n-alkanals and trans-2-alkenals (group II aldehydes derived from both MUFA and PUFA hydroperoxides) strongly and positively loaded on PC2*. PCR analysis of these scores vectors (SVs) demonstrated that PCs 1 (positively-loaded linoleoylglycerols and [linoleoylglycerol]:[SFA] content ratio), 2 (positively-loaded oleoylglycerols and negatively-loaded SFAs), 3 (positively-loaded linolenoylglycerols and [PUFA]:[SFA] content ratios), and 4 (exclusively orthogonal sampling time-points) all powerfully contributed to aldehydic PC1* SVs (p 10-3 to < 10-9), as did all PC1-3 x PC4 interaction ones (p 10-5 to < 10-9). PC2* was also markedly dependent on all the above PC SVs (PC2 > PC1 and PC3), and the interactions of PC1 and PC2 with PC4 (p < 10-9 in each case), but not the PC3 x PC4 contribution. Conclusions: NMR-linked PCR analysis is a valuable strategy for (1) modelling the generation of aldehydic LOPs in heated cooking oils and other FM, and (2) tracking their unsaturated fatty acid (UFA) triacylglycerol sources therein.

Keywords: frying oils, lipid oxidation products, frying episodes, chemometrics, principal component regression, NMR Analysis, cytotoxic/genotoxic aldehydes

Procedia PDF Downloads 144
270 Hygrothermal Interactions and Energy Consumption in Cold Climate Hospitals: Integrating Numerical Analysis and Case Studies to Investigate and Analyze the Impact of Air Leakage and Vapor Retarding

Authors: Amir E. Amirzadeh, Richard K. Strand

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Moisture-induced problems are a significant concern for building owners, architects, construction managers, and building engineers, as they can have substantial impacts on building enclosures' durability and performance. Computational analyses, such as hygrothermal and thermal analysis, can provide valuable information and demonstrate the expected relative performance of building enclosure systems but are not grounded in absolute certainty. This paper evaluates the hygrothermal performance of common enclosure systems in hospitals in cold climates. The study aims to investigate the impact of exterior wall systems on hospitals, focusing on factors such as durability, construction deficiencies, and energy performance. The study primarily examines the impact of air leakage and vapor retarding layers relative to energy consumption. While these factors have been studied in residential and commercial buildings, there is a lack of information on their impact on hospitals in a holistic context. The study integrates various research studies and professional experience in hospital building design to achieve its objective. The methodology involves surveying and observing exterior wall assemblies, reviewing common exterior wall assemblies and details used in hospital construction, performing simulations and numerical analyses of various variables, validating the model and mechanism using available data from industry and academia, visualizing the outcomes of the analysis, and developing a mechanism to demonstrate the relative performance of exterior wall systems for hospitals under specific conditions. The data sources include case studies from real-world projects and peer-reviewed articles, industry standards, and practices. This research intends to integrate and analyze the in-situ and as-designed performance and durability of building enclosure assemblies with numerical analysis. The study's primary objective is to provide a clear and precise roadmap to better visualize and comprehend the correlation between the durability and performance of common exterior wall systems used in the construction of hospitals and the energy consumption of these buildings under certain static and dynamic conditions. As the construction of new hospitals and renovation of existing ones have grown over the last few years, it is crucial to understand the effect of poor detailing or construction deficiencies on building enclosure systems' performance and durability in healthcare buildings. This study aims to assist stakeholders involved in hospital design, construction, and maintenance in selecting durable and high-performing wall systems. It highlights the importance of early design evaluation, regular quality control during the construction of hospitals, and understanding the potential impacts of improper and inconsistent maintenance and operation practices on occupants, owner, building enclosure systems, and Heating, Ventilation, and Air Conditioning (HVAC) systems, even if they are designed to meet the project requirements.

Keywords: hygrothermal analysis, building enclosure, hospitals, energy efficiency, optimization and visualization, uncertainty and decision making

Procedia PDF Downloads 41
269 Achieving Flow at Work: An Experience Sampling Study to Comprehend How Cognitive Task Characteristics and Work Environments Predict Flow Experiences

Authors: Jonas De Kerf, Rein De Cooman, Sara De Gieter

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For many decades, scholars have aimed to understand how work can become more meaningful by maximizing both potential and enhancing feelings of satisfaction. One of the largest contributions towards such positive psychology was made with the introduction of the concept of ‘flow,’ which refers to a condition in which people feel intense engagement and effortless action. Since then, valuable research on work-related flow has indicated that this state of mind is related to positive outcomes for both organizations (e.g., social, supportive climates) and workers (e.g., job satisfaction). Yet, scholars still do not fully comprehend how such deep involvement at work is obtained, given the notion that flow is considered a short-term, complex, and dynamic experience. Most research neglects that people who experience flow ought to be optimally challenged so that intense concentration is required. Because attention is at the core of this enjoyable state of mind, this study aims to comprehend how elements that affect workers’ cognitive functioning impact flow at work. Research on cognitive performance suggests that working on mentally demanding tasks (e.g., information processing tasks) requires workers to concentrate deeply, as a result leading to flow experiences. Based on social facilitation theory, working on such tasks in an isolated environment eases concentration. Prior research has indicated that working at home (instead of working at the office) or in a closed office (rather than in an open-plan office) impacts employees’ overall functioning in terms of concentration and productivity. Consequently, we advance such knowledge and propose an interaction by combining cognitive task characteristics and work environments among part-time teleworkers. Hence, we not only aim to shed light on the relation between cognitive tasks and flow but also provide empirical evidence that workers performing such tasks achieve the highest states of flow while working either at home or in closed offices. In July 2022, an experience-sampling study will be conducted that uses a semi-random signal schedule to understand how task and environment predictors together impact part-time teleworkers’ flow. More precisely, about 150 knowledge workers will fill in multiple surveys a day for two consecutive workweeks to report their flow experiences, cognitive tasks, and work environments. Preliminary results from a pilot study indicate that on a between level, tasks high in information processing go along with high self-reported fluent productivity (i.e., making progress). As expected, evidence was found for higher fluency in productivity for workers performing information processing tasks both at home and in a closed office, compared to those performing the same tasks at the office or in open-plan offices. This study expands the current knowledge on work-related flow by looking at a task and environmental predictors that enable workers to obtain such a peak state. While doing so, our findings suggest that practitioners should strive for ideal alignments between tasks and work locations to work with both deep involvement and gratification.

Keywords: cognitive work, office lay-out, work location, work-related flow

Procedia PDF Downloads 66
268 Integration of a Protective Film to Enhance the Longevity and Performance of Miniaturized Ion Sensors

Authors: Antonio Ruiz Gonzalez, Kwang-Leong Choy

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The measurement of electrolytes has a high value in the clinical routine. Ions are present in all body fluids with variable concentrations and are involved in multiple pathologies such as heart failures and chronic kidney disease. In the case of dissolved potassium, although a high concentration in the blood (hyperkalemia) is relatively uncommon in the general population, it is one of the most frequent acute electrolyte abnormalities. In recent years, the integration of thin films technologies in this field has allowed the development of highly sensitive biosensors with ultra-low limits of detection for the assessment of metals in liquid samples. However, despite the current efforts in the miniaturization of sensitive devices and their integration into portable systems, only a limited number of successful examples used commercially can be found. This fact can be attributed to a high cost involved in their production and the sustained degradation of the electrodes over time, which causes a signal drift in the measurements. Thus, there is an unmet necessity for the development of low-cost and robust sensors for the real-time monitoring of analyte concentrations in patients to allow the early detection and diagnosis of diseases. This paper reports a thin film ion-selective sensor for the evaluation of potassium ions in aqueous samples. As an alternative for this fabrication method, aerosol assisted chemical vapor deposition (AACVD), was applied due to cost-effectivity and fine control over the film deposition. Such a technique does not require vacuum and is suitable for the coating of large surface areas and structures with complex geometries. This approach allowed the fabrication of highly homogeneous surfaces with well-defined microstructures onto 50 nm thin gold layers. The degradative processes of the ubiquitously employed poly (vinyl chloride) membranes in contact with an electrolyte solution were studied, including the polymer leaching process, mechanical desorption of nanoparticles and chemical degradation over time. Rational design of a protective coating based on an organosilicon material in combination with cellulose to improve the long-term stability of the sensors was then carried out, showing an improvement in the performance after 5 weeks. The antifouling properties of such coating were assessed using a cutting-edge quartz microbalance sensor, allowing the quantification of the adsorbed proteins in the nanogram range. A correlation between the microstructural properties of the films with the surface energy and biomolecules adhesion was then found and used to optimize the protective film.

Keywords: hyperkalemia, drift, AACVD, organosilicon

Procedia PDF Downloads 102
267 Application of Harris Hawks Optimization Metaheuristic Algorithm and Random Forest Machine Learning Method for Long-Term Production Scheduling Problem under Uncertainty in Open-Pit Mines

Authors: Kamyar Tolouei, Ehsan Moosavi

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In open-pit mines, the long-term production scheduling optimization problem (LTPSOP) is a complicated problem that contains constraints, large datasets, and uncertainties. Uncertainty in the output is caused by several geological, economic, or technical factors. Due to its dimensions and NP-hard nature, it is usually difficult to find an ideal solution to the LTPSOP. The optimal schedule generally restricts the ore, metal, and waste tonnages, average grades, and cash flows of each period. Past decades have witnessed important measurements of long-term production scheduling and optimal algorithms since researchers have become highly cognizant of the issue. In fact, it is not possible to consider LTPSOP as a well-solved problem. Traditional production scheduling methods in open-pit mines apply an estimated orebody model to produce optimal schedules. The smoothing result of some geostatistical estimation procedures causes most of the mine schedules and production predictions to be unrealistic and imperfect. With the expansion of simulation procedures, the risks from grade uncertainty in ore reserves can be evaluated and organized through a set of equally probable orebody realizations. In this paper, to synthesize grade uncertainty into the strategic mine schedule, a stochastic integer programming framework is presented to LTPSOP. The objective function of the model is to maximize the net present value and minimize the risk of deviation from the production targets considering grade uncertainty simultaneously while satisfying all technical constraints and operational requirements. Instead of applying one estimated orebody model as input to optimize the production schedule, a set of equally probable orebody realizations are applied to synthesize grade uncertainty in the strategic mine schedule and to produce a more profitable and risk-based production schedule. A mixture of metaheuristic procedures and mathematical methods paves the way to achieve an appropriate solution. This paper introduced a hybrid model between the augmented Lagrangian relaxation (ALR) method and the metaheuristic algorithm, the Harris Hawks optimization (HHO), to solve the LTPSOP under grade uncertainty conditions. In this study, the HHO is experienced to update Lagrange coefficients. Besides, a machine learning method called Random Forest is applied to estimate gold grade in a mineral deposit. The Monte Carlo method is used as the simulation method with 20 realizations. The results specify that the progressive versions have been considerably developed in comparison with the traditional methods. The outcomes were also compared with the ALR-genetic algorithm and ALR-sub-gradient. To indicate the applicability of the model, a case study on an open-pit gold mining operation is implemented. The framework displays the capability to minimize risk and improvement in the expected net present value and financial profitability for LTPSOP. The framework could control geological risk more effectively than the traditional procedure considering grade uncertainty in the hybrid model framework.

Keywords: grade uncertainty, metaheuristic algorithms, open-pit mine, production scheduling optimization

Procedia PDF Downloads 73
266 Growth and Differentiation of Mesenchymal Stem Cells on Titanium Alloy Ti6Al4V and Novel Beta Titanium Alloy Ti36Nb6Ta

Authors: Eva Filová, Jana Daňková, Věra Sovková, Matej Daniel

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Titanium alloys are biocompatible metals that are widely used in clinical practice as load bearing implants. The chemical modification may influence cell adhesion, proliferation, and differentiation as well as stiffness of the material. The aim of the study was to evaluate the adhesion, growth and differentiation of pig mesenchymal stem cells on the novel beta titanium alloy Ti36Nb6Ta compared to standard medical titanium alloy Ti6Al4V. Discs of Ti36Nb6Ta and Ti6Al4V alloy were sterilized by ethanol, put in 48-well plates, and seeded by pig mesenchymal stem cells at the density of 60×103/cm2 and cultured in Minimum essential medium (Sigma) supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell viability was evaluated using MTS assay (CellTiter 96® AQueous One Solution Cell Proliferation Assay;Promega), cell proliferation using Quant-iT™ ds DNA Assay Kit (Life Technologies). Cells were stained immunohistochemically using monoclonal antibody beta-actin, and secondary antibody conjugated with AlexaFluor®488 and subsequently the spread area of cells was measured. Cell differentiation was evaluated by alkaline phosphatase assay using p-nitrophenyl phosphate (pNPP) as a substrate; the reaction was stopped by NaOH, and the absorbance was measured at 405 nm. Osteocalcin, specific bone marker was stained immunohistochemically and subsequently visualized using confocal microscopy; the fluorescence intensity was analyzed and quantified. Moreover, gene expression of osteogenic markers osteocalcin and type I collagen was evaluated by real-time reverse transcription-PCR (qRT-PCR). For statistical evaluation, One-way ANOVA followed by Student-Newman-Keuls Method was used. For qRT-PCR, the nonparametric Kruskal-Wallis Test and Dunn's Multiple Comparison Test were used. The absorbance in MTS assay was significantly higher on titanium alloy Ti6Al4V compared to beta titanium alloy Ti36Nb6Ta on days 7 and 14. Mesenchymal stem cells were well spread on both alloys, but no difference in spread area was found. No differences in alkaline phosphatase assay, fluorescence intensity of osteocalcin as well as the expression of type I collagen, and osteocalcin genes were observed. Higher expression of type I collagen compared to osteocalcin was observed for cells on both alloys. Both beta titanium alloy Ti36Nb6Ta and titanium alloy Ti6Al4V Ti36Nb6Ta supported mesenchymal stem cellsˈ adhesion, proliferation and osteogenic differentiation. Novel beta titanium alloys Ti36Nb6Ta is a promising material for bone implantation. The project was supported by the Czech Science Foundation: grant No. 16-14758S, the Grant Agency of the Charles University, grant No. 1246314 and by the Ministry of Education, Youth and Sports NPU I: LO1309.

Keywords: beta titanium, cell growth, mesenchymal stem cells, titanium alloy, implant

Procedia PDF Downloads 295
265 Novel Aspects of Merger Control Pertaining to Nascent Acquisition: An Analytical Legal Research

Authors: Bhargavi G. Iyer, Ojaswi Bhagat

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It is often noted that the value of a novel idea lies in its successful implementation. However, successful implementation requires the nurturing and encouragement of innovation. Nascent competitors are a true representation of innovation in any given industry. A nascent competitor is an entity whose prospective innovation poses a future threat to an incumbent dominant competitor. While a nascent competitor benefits in several ways, it is also exposed significantly and is at greater risk of facing the brunt of exclusionary practises and abusive conduct by dominant incumbent competitors in the industry. This research paper aims to explore the risks and threats faced by nascent competitors and analyse the benefits they accrue as well as the advantages they proffer to the economy; through an analytical, critical study. In such competitive market environments, a rise of the acquisitions of nascent competitors by the incumbent dominants is observed. Therefore, this paper will examine the dynamics of nascent acquisition. Further, this paper hopes to specifically delve into the role of antitrust bodies in regulating nascent acquisition. This paper also aspires to deal with the question how to distinguish harmful from harmless acquisitions in order to facilitate ideal enforcement practice. This paper proposes mechanisms of scrutiny in order to ensure healthy market practises and efficient merger control in the context of nascent acquisitions. Taking into account the scope and nature of the topic, as well as the resources available and accessible, a combination of the methods of doctrinal research and analytical research were employed, utilising secondary sources in order to assess and analyse the subject of research. While legally evaluating the Killer Acquisition theory and the Nascent Potential Acquisition theory, this paper seeks to critically survey the precedents and instances of nascent acquisitions. In addition to affording a compendious account of the legislative framework and regulatory mechanisms in the United States, the United Kingdom, and the European Union; it hopes to suggest an internationally practicable legal foundation for domestic legislation and enforcement to adopt. This paper hopes to appreciate the complexities and uncertainties with respect to nascent acquisitions and attempts to suggest viable and plausible policy measures in antitrust law. It additionally attempts to examine the effects of such nascent acquisitions upon the consumer and the market economy. This paper weighs the argument of shifting the evidentiary burden on to the merging parties in order to improve merger control and regulation and expounds on its discovery of the strengths and weaknesses of the approach. It is posited that an effective combination of factual, legal, and economic analysis of both the acquired and acquiring companies possesses the potential to improve ex post and ex ante merger review outcomes involving nascent companies; thus, preventing anti-competitive practises. This paper concludes with an analysis of the possibility and feasibility of industry-specific identification of anti-competitive nascent acquisitions and implementation of measures accordingly.

Keywords: acquisition, antitrust law, exclusionary practises merger control, nascent competitor

Procedia PDF Downloads 133
264 Gender Differences in Morbid Obese Children: Clinical Significance of Two Diagnostic Obesity Notation Model Assessment Indices

Authors: Mustafa M. Donma, Orkide Donma, Murat Aydin, Muhammet Demirkol, Burcin Nalbantoglu, Aysin Nalbantoglu, Birol Topcu

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Childhood obesity is an ever increasing global health problem, affecting both developed and developing countries. Accurate evaluation of obesity in children requires difficult and detailed investigation. In our study, obesity in children was evaluated using new body fat ratios and indices. Assessment of anthropometric measurements, as well as some ratios, is important because of the evaluation of gender differences particularly during the late periods of obesity. A total of 239 children; 168 morbid obese (MO) (81 girls and 87 boys) and 71 normal weight (NW) (40 girls and 31 boys) children, participated in the study. Informed consent forms signed by the parents were obtained. Ethics Committee approved the study protocol. Mean ages (years)±SD calculated for MO group were 10.8±2.9 years in girls and 10.1±2.4 years in boys. The corresponding values for NW group were 9.0±2.0 years in girls and 9.2±2.1 years in boys. Mean body mass index (BMI)±SD values for MO group were 29.1±5.4 kg/m2 and 27.2±3.9 kg/m2 in girls and boys, respectively. These values for NW group were calculated as 15.5±1.0 kg/m2 in girls and 15.9±1.1 kg/m2 in boys. Groups were constituted based upon BMI percentiles for age-and-sex values recommended by WHO. Children with percentiles >99 were grouped as MO and children with percentiles between 85 and 15 were considered NW. The anthropometric measurements were recorded and evaluated along with the new ratios such as trunk-to-appendicular fat ratio, as well as indices such as Index-I and Index-II. The body fat percent values were obtained by bio-electrical impedance analysis. Data were entered into a database for analysis using SPSS/PASW 18 Statistics for Windows statistical software. Increased waist-to-hip circumference (C) ratios, decreased head-to-neck C, height ‘to’ ‘two’-‘to’-waist C and height ‘to’ ‘two’-‘to’-hip C ratios were observed in parallel with the development of obesity (p≤0.001). Reference value for height ‘to’ ‘two’-‘to’-hip ratio was detected as approximately 1.0. Index-II, based upon total body fat mass, showed much more significant differences between the groups than Index-I based upon weight. There was not any difference between trunk-to-appendicular fat ratios of NW girls and NW boys (p≥0.05). However, significantly increased values for MO girls in comparison with MO boys were observed (p≤0.05). This parameter showed no difference between NW and MO states in boys (p≥0.05). However, statistically significant increase was noted in MO girls compared to their NW states (p≤0.001). Trunk-to-appendicular fat ratio was the only fat-based parameter, which showed gender difference between NW and MO groups. This study has revealed that body ratios and formula based upon body fat tissue are more valuable parameters than those based on weight and height values for the evaluation of morbid obesity in children.

Keywords: anthropometry, childhood obesity, gender, morbid obesity

Procedia PDF Downloads 300
263 Magnetic Carriers of Organic Selenium (IV) Compounds: Physicochemical Properties and Possible Applications in Anticancer Therapy

Authors: E. Mosiniewicz-Szablewska, P. Suchocki, P. C. Morais

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Despite the significant progress in cancer treatment, there is a need to search for new therapeutic methods in order to minimize side effects. Chemotherapy, the main current method of treating cancer, is non-selective and has a number of limitations. Toxicity to healthy cells is undoubtedly the biggest problem limiting the use of many anticancer drugs. The problem of how to kill cancer without harming a patient can be solved by using organic selenium (IV) compounds. Organic selenium (IV) compounds are a new class of materials showing a strong anticancer activity. They are first organic compounds containing selenium at the +4 oxidation level and therefore they eliminate the multidrug-resistance for all tumor cell lines tested so far. These materials are capable of selectively killing cancer cells without damaging the healthy ones. They are obtained by the incorporation of selenous acid (H2SeO3) into molecules of fatty acids of sunflower oil and therefore, they are inexpensive to manufacture. Attaching these compounds to magnetic carriers enables their precise delivery directly to the tumor area and the simultaneous application of the magnetic hyperthermia, thus creating a huge opportunity to effectively get rid of the tumor without any side effects. Polylactic-co-glicolic acid (PLGA) nanocapsules loaded with maghemite (-Fe2O3) nanoparticles and organic selenium (IV) compounds are successfully prepared by nanoprecipitation method. In vitro antitumor activity of the nanocapsules were evidenced using murine melanoma (B16-F10), oral squamos carcinoma (OSCC) and murine (4T1) and human (MCF-7) breast lines. Further exposure of these cells to an alternating magnetic field increased the antitumor effect of nanocapsules. Moreover, the nanocapsules presented antitumor effect while not affecting normal cells. Magnetic properties of the nanocapsules were investigated by means of dc magnetization, ac susceptibility and electron spin resonance (ESR) measurements. The nanocapsules presented a typical superparamagnetic behavior around room temperature manifested itself by the split between zero field-cooled/field-cooled (ZFC/FC) magnetization curves and the absence of hysteresis on the field-dependent magnetization curve above the blocking temperature. Moreover, the blocking temperature decreased with increasing applied magnetic field. The superparamagnetic character of the nanocapsules was also confirmed by the occurrence of a maximum in temperature dependences of both real ′(T) and imaginary ′′ (T) components of the ac magnetic susceptibility, which shifted towards higher temperatures with increasing frequency. Additionally, upon decreasing the temperature the ESR signal shifted to lower fields and gradually broadened following closely the predictions for the ESR of superparamagnetoc nanoparticles. The observed superparamagnetic properties of nanocapsules enable their simple manipulation by means of magnetic field gradient, after introduction into the blood stream, which is a necessary condition for their use as magnetic drug carriers. The observed anticancer and superparamgnetic properties show that the magnetic nanocapsules loaded with organic selenium (IV) compounds should be considered as an effective material system for magnetic drug delivery and magnetohyperthermia inductor in antitumor therapy.

Keywords: cancer treatment, magnetic drug delivery system, nanomaterials, nanotechnology

Procedia PDF Downloads 177
262 Use of PACER Application as Physical Activity Assessment Tool: Results of a Reliability and Validity Study

Authors: Carine Platat, Fatima Qshadi, Ghofran Kayed, Nour Hussein, Amjad Jarrar, Habiba Ali

Abstract:

Nowadays, smartphones are very popular. They are offering a variety of easy-to-use and free applications among which step counters and fitness tests. The number of users is huge making of such applications a potentially efficient new strategy to encourage people to become more active. Nonetheless, data on their reliability and validity are very scarce and when available, they are often negative and contradictory. Besides, weight status, which is likely to introduce a bias in the physical activity assessment, was not often considered. Hence, the use of these applications as motivational tool, assessment tool and in research is questionable. PACER is one of the free step counters application. Even though it is one of the best rated free application by users, it has never been tested for reliability and validity. Prior any use of PACER, this remains to be investigated. The objective of this work is to investigate the reliability and validity of the smartphone application PACER in measuring the number of steps and in assessing the cardiorespiratory fitness by the 6 minutes walking test. 20 overweight or obese students (10 male and 10 female) were recruited at the United Arab Emirate University, aged between 18 and 25 years old. Reliability and validity were tested in real life conditions and in controlled conditions by using a treadmill. Test-retest experiments were done with PACER on 2 days separated by a week in real life conditions (24 hours each time) and in controlled conditions (30 minutes on treadmill, 3km/h). Validity was tested against the pedometer OMRON in the same conditions. During treadmill test, video was recorded and steps numbers were compared between PACER, pedometer and video. The validity of PACER in estimating the cardiorespiratory fitness (VO2max) as part of the 6 minutes walking test (6MWT) was studied against the 20m shuttle running test. Reliability was studied by calculating intraclass correlation coefficients (ICC), 95% confidence interval (95%CI) and by Bland-Altman plots. Validity was studied by calculating Spearman correlation coefficient (rho) and Bland-Altman plots. PACER reliability was good in both male and female in real life conditions (p≤10-3) but only in female in controlled conditions (p=0.01). PACER was valid against OMRON pedometer in male and female in real life conditions (rho=0.94, p≤10-3 ; rho=0.64, p=0.01, in male and female respectively). In controlled conditions, PACER was not valid against pedometer. But, PACER was valid against video in female (rho=0.72, p≤10-3). PACER was valid against the shuttle run test in male and female (rho-=0.66, p=0.01 ; rho=0.51, p=0.04) to estimate VO2max. This study provides data on the reliability and viability of PACER in overweight or obese male and female young adults. Globally, PACER was shown as reliable and valid in real life conditions in overweight or obese male and female to count steps and assess fitness. This supports the use of PACER to assess and promote physical activity in clinical follow-up and community interventions.

Keywords: smartphone application, pacer, reliability, validity, steps, fitness, physical activity

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261 Automated End of Sprint Detection for Force-Velocity-Power Analysis with GPS/GNSS Systems

Authors: Patrick Cormier, Cesar Meylan, Matt Jensen, Dana Agar-Newman, Chloe Werle, Ming-Chang Tsai, Marc Klimstra

Abstract:

Sprint-derived horizontal force-velocity-power (FVP) profiles can be developed with adequate validity and reliability with satellite (GPS/GNSS) systems. However, FVP metrics are sensitive to small nuances in data processing procedures such that minor differences in defining the onset and end of the sprint could result in different FVP metric outcomes. Furthermore, in team-sports, there is a requirement for rapid analysis and feedback of results from multiple athletes, therefore developing standardized and automated methods to improve the speed, efficiency and reliability of this process are warranted. Thus, the purpose of this study was to compare different methods of sprint end detection on the development of FVP profiles from 10Hz GPS/GNSS data through goodness-of-fit and intertrial reliability statistics. Seventeen national team female soccer players participated in the FVP protocol which consisted of 2x40m maximal sprints performed towards the end of a soccer specific warm-up in a training session (1020 hPa, wind = 0, temperature = 30°C) on an open grass field. Each player wore a 10Hz Catapult system unit (Vector S7, Catapult Innovations) inserted in a vest in a pouch between the scapulae. All data were analyzed following common procedures. Variables computed and assessed were the model parameters, estimated maximal sprint speed (MSS) and the acceleration constant τ, in addition to horizontal relative force (F₀), velocity at zero (V₀), and relative mechanical power (Pmax). The onset of the sprints was standardized with an acceleration threshold of 0.1 m/s². The sprint end detection methods were: 1. Time when peak velocity (MSS) was achieved (zero acceleration), 2. Time after peak velocity drops by -0.4 m/s, 3. Time after peak velocity drops by -0.6 m/s, and 4. When the integrated distance from the GPS/GNSS signal achieves 40-m. Goodness-of-fit of each sprint end detection method was determined using the residual sum of squares (RSS) to demonstrate the error of the FVP modeling with the sprint data from the GPS/GNSS system. Inter-trial reliability (from 2 trials) was assessed utilizing intraclass correlation coefficients (ICC). For goodness-of-fit results, the end detection technique that used the time when peak velocity was achieved (zero acceleration) had the lowest RSS values, followed by -0.4 and -0.6 velocity decay, and 40-m end had the highest RSS values. For intertrial reliability, the end of sprint detection techniques that were defined as the time at (method 1) or shortly after (method 2 and 3) when MSS was achieved had very large to near perfect ICC and the time at the 40 m integrated distance (method 4) had large to very large ICCs. Peak velocity was reached at 29.52 ± 4.02-m. Therefore, sport scientists should implement end of sprint detection either when peak velocity is determined or shortly after to improve goodness of fit to achieve reliable between trial FVP profile metrics. Although, more robust processing and modeling procedures should be developed in future research to improve sprint model fitting. This protocol was seamlessly integrated into the usual training which shows promise for sprint monitoring in the field with this technology.

Keywords: automated, biomechanics, team-sports, sprint

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260 More Than Financial Wealth: An Empirical Study on the Impact of Family Involvement on the Dimensions of Exit Success

Authors: Tim Vollmer, Andrea Greven, Malte Brettel

Abstract:

Family firms represent the predominant business structure worldwide, accounting for 90 percent of all operational businesses. These firms are essential to society and the economy. In the past decade, family firm exits increased by 72%; and in the next five years, 95,000 German family firms will be sold, acquired, or liquidated. For family firms, socioemotional wealth represents the frame of reference and value to preserve when making decisions. Family firm exits threaten the socioemotional wealth, as in extreme scenarios, economic logic may take over. So, a dilemma arises: Maintaining socioemotional wealth versus pursuing financial wealth. Family firm researchers agree that family involvement leads to specific goals, behaviors, and outcomes. For instance, the desire to protect socioemotional wealth when selling the firm and the focus on particular exit success dimensions, depending on the family's role inside the firm. However, despite the regularity of family firm exits, there is little research on the effect of family involvement on the family firm CEOs' perceived exit performance. We investigate the family firm CEOs' perceived exit performance, which we call exit success. Considering the deficiencies in the literature, we identify two research gaps. First, it remains unclear how family involvement affects the dimensions of exit success. Hence, we provide evidence of which success dimensions matter most depending on the family's involvement and how to differentiate successful from unsuccessful exits. Second, prior work has analyzed family involvement in the socioemotional wealth context but found contradictory findings. This work considers, for example, the family generation in control and identifies the tipping point of economic objectives becoming preferable over socioemotional wealth-related goals. This paper theorizes and empirically investigates, through the lens of socioemotional wealth and conflict theory, how socioemotional wealth mediates the relationship between family involvement and family firms' exit success. We analyze family firms' exit success dimensions of personal financial benefits, personal reputation, employee benefits, and firm mission persistence. Family involvement considers the family firms' heterogeneity in ownership, management, and generation. We use a quantitative approach in the form of an online survey by drawing on 116 responses from former family firm CEOs'. This study highlights that socioemotional wealth mediates the relationship between the dimensions of family involvement and exit success. The greater socioemotional wealth, the greater the family firm CEOs focus on the pro-organizational exit success dimensions of employee benefits and firm mission persistence. In contrast, the self-regarding dimension of personal financial benefits is significantly negatively affected. An important finding is that later generations and the number of family managers involved significantly negatively affect the two pro-organizational dimensions of exit success. Family ownership does not show any significant effect. Our work widens implications for research, theory, and practice by contributing in two meaningful ways. First, our results offer insights to differentiate successful from unsuccessful family firm exits and provide evidence of which success dimensions matter and which to focus on, most dependent on the family's role inside the firm. Second, our article advances research and empirical understanding of family firms and socioemotional wealth by clarifying contradictory findings.

Keywords: exit success, family firm exit, perceived exit performance, socioemotional wealth

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259 Screening Tools and Its Accuracy for Common Soccer Injuries: A Systematic Review

Authors: R. Christopher, C. Brandt, N. Damons

Abstract:

Background: The sequence of prevention model states that by constant assessment of injury, injury mechanisms and risk factors are identified, highlighting that collecting and recording of data is a core approach for preventing injuries. Several screening tools are available for use in the clinical setting. These screening techniques only recently received research attention, hence there is a dearth of inconsistent and controversial data regarding their applicability, validity, and reliability. Several systematic reviews related to common soccer injuries have been conducted; however, none of them addressed the screening tools for common soccer injuries. Objectives: The purpose of this study was to conduct a review of screening tools and their accuracy for common injuries in soccer. Methods: A systematic scoping review was performed based on the Joanna Briggs Institute procedure for conducting systematic reviews. Databases such as SPORT Discus, Cinahl, Medline, Science Direct, PubMed, and grey literature were used to access suitable studies. Some of the key search terms included: injury screening, screening, screening tool accuracy, injury prevalence, injury prediction, accuracy, validity, specificity, reliability, sensitivity. All types of English studies dating back to the year 2000 were included. Two blind independent reviewers selected and appraised articles on a 9-point scale for inclusion as well as for the risk of bias with the ACROBAT-NRSI tool. Data were extracted and summarized in tables. Plot data analysis was done, and sensitivity and specificity were analyzed with their respective 95% confidence intervals. I² statistic was used to determine the proportion of variation across studies. Results: The initial search yielded 95 studies, of which 21 were duplicates, and 54 excluded. A total of 10 observational studies were included for the analysis: 3 studies were analysed quantitatively while the remaining 7 were analysed qualitatively. Seven studies were graded low and three studies high risk of bias. Only high methodological studies (score > 9) were included for analysis. The pooled studies investigated tools such as the Functional Movement Screening (FMS™), the Landing Error Scoring System (LESS), the Tuck Jump Assessment, the Soccer Injury Movement Screening (SIMS), and the conventional hamstrings to quadriceps ratio. The accuracy of screening tools was of high reliability, sensitivity and specificity (calculated as ICC 0.68, 95% CI: 52-0.84; and 0.64, 95% CI: 0.61-0.66 respectively; I² = 13.2%, P=0.316). Conclusion: Based on the pooled results from the included studies, the FMS™ has a good inter-rater and intra-rater reliability. FMS™ is a screening tool capable of screening for common soccer injuries, and individual FMS™ scores are a better determinant of performance in comparison with the overall FMS™ score. Although meta-analysis could not be done for all the included screening tools, qualitative analysis also indicated good sensitivity and specificity of the individual tools. Higher levels of evidence are, however, needed for implication in evidence-based practice.

Keywords: accuracy, screening tools, sensitivity, soccer injuries, specificity

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258 Functional Analysis of Variants Implicated in Hearing Loss in a Cohort from Argentina: From Molecular Diagnosis to Pre-Clinical Research

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

Abstract:

Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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257 Machine Learning Framework: Competitive Intelligence and Key Drivers Identification of Market Share Trends among Healthcare Facilities

Authors: Anudeep Appe, Bhanu Poluparthi, Lakshmi Kasivajjula, Udai Mv, Sobha Bagadi, Punya Modi, Aditya Singh, Hemanth Gunupudi, Spenser Troiano, Jeff Paul, Justin Stovall, Justin Yamamoto

Abstract:

The necessity of data-driven decisions in healthcare strategy formulation is rapidly increasing. A reliable framework which helps identify factors impacting a healthcare provider facility or a hospital (from here on termed as facility) market share is of key importance. This pilot study aims at developing a data-driven machine learning-regression framework which aids strategists in formulating key decisions to improve the facility’s market share which in turn impacts in improving the quality of healthcare services. The US (United States) healthcare business is chosen for the study, and the data spanning 60 key facilities in Washington State and about 3 years of historical data is considered. In the current analysis, market share is termed as the ratio of the facility’s encounters to the total encounters among the group of potential competitor facilities. The current study proposes a two-pronged approach of competitor identification and regression approach to evaluate and predict market share, respectively. Leveraged model agnostic technique, SHAP, to quantify the relative importance of features impacting the market share. Typical techniques in literature to quantify the degree of competitiveness among facilities use an empirical method to calculate a competitive factor to interpret the severity of competition. The proposed method identifies a pool of competitors, develops Directed Acyclic Graphs (DAGs) and feature level word vectors, and evaluates the key connected components at the facility level. This technique is robust since its data-driven, which minimizes the bias from empirical techniques. The DAGs factor in partial correlations at various segregations and key demographics of facilities along with a placeholder to factor in various business rules (for ex. quantifying the patient exchanges, provider references, and sister facilities). Identified are the multiple groups of competitors among facilities. Leveraging the competitors' identified developed and fine-tuned Random Forest Regression model to predict the market share. To identify key drivers of market share at an overall level, permutation feature importance of the attributes was calculated. For relative quantification of features at a facility level, incorporated SHAP (SHapley Additive exPlanations), a model agnostic explainer. This helped to identify and rank the attributes at each facility which impacts the market share. This approach proposes an amalgamation of the two popular and efficient modeling practices, viz., machine learning with graphs and tree-based regression techniques to reduce the bias. With these, we helped to drive strategic business decisions.

Keywords: competition, DAGs, facility, healthcare, machine learning, market share, random forest, SHAP

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256 Bone Mineralization in Children with Wilson’s Disease

Authors: Shiamaa Eltantawy, Gihan Sobhy, Alif Alaam

Abstract:

Wilson disease, or hepatolenticular degeneration, is an autosomal recessive disease that results in excess copper buildup in the body. It primarily affects the liver and basal ganglia of the brain, but it can affect other organ systems. Musculoskeletal abnormalities, including premature osteoarthritis, skeletal deformity, and pathological bone fractures, can occasionally be found in WD patients with a hepatic or neurologic type. The aim was to assess the prevalence of osteoporosis and osteopenia in Wilson’s disease patients. This case-control study was conducted on ninety children recruited from the inpatient ward and outpatient clinic of the Paediatric Hepatology, Gastroenterology, and Nutrition department of the National Liver Institute at Menofia University, aged from 1 to 18 years. Males were 49, and females were 41. Children were divided into three groups: (Group I) consisted of thirty patients with WD; (Group II) consisted of thirty patients with chronic liver disease other than WD; (Group III) consisted of thirty age- and sex-matched healthy The exclusion criteria were patients with hyperparathyroidism, hyperthyroidism, renal failure, Cushing's syndrome, and patients on certain drugs such as chemotherapy, anticonvulsants, or steroids. All patients were subjected to the following: 1- Full history-taking and clinical examination. 2-Laboratory investigations: (FBC,ALT,AST,serum albumin, total protein, total serum bilirubin,direct bilirubin,alkaline phosphatase, prothrombin time, serum critine,parathyroid hormone, serum calcium, serum phosphrus). 3-Bone mineral density (BMD, gm/cm2) values were measured by dual-energy X-ray absorptiometry (DEXA). The results revealed that there was a highly statistically significant difference between the three groups regarding the DEXA scan, and there was no statistically significant difference between groups I and II, but the WD group had the lowest bone mineral density. The WD group had a large number of cases of osteopenia and osteoporosis, but there was no statistically significant difference with the group II mean, while a high statistically significant difference was found when compared to group III. In the WD group, there were 20 patients with osteopenia, 4 patients with osteoporosis, and 6 patients who were normal. The percentages were 66.7%, 13.3%, and 20%, respectively. Therefore, the largest number of cases in the WD group had osteopenia. There was no statistically significant difference found between WD patients on different treatment regimens regarding DEXA scan results (Z-Score). There was no statistically significant difference found between patients in the WD group (normal, osteopenic, or osteoporotic) regarding phosphorus (mg/dL), but there was a highly statistically significant difference found between them regarding ionised Ca (mmol/L). Therefore, there was a decrease in bone mineral density when the Ca level was decreased. In summary, Wilson disease is associated with bone demineralization. The largest number of cases in the WD group in our study had osteopenia (66.7%). Different treatment regimens (zinc monotherapy, Artamin, and zinc) as well as different laboratory parameters have no effect on bone mineralization in WD cases. Decreased ionised Ca is associated with low BMD in WD patients. Children with WD should be investigated for BMD.

Keywords: wilson disease, Bone mineral density, liver disease, osteoporosis

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